We have shown that rabbit macrophages make at least two chemically and immunologically distinct endogenous pyrongens. These pyrogens have been radio labelled using 3H and 14C amino acids, and we have raised an antibody to one of them. Both pyrogens appear to have lymphocyte activating factor (LAF) activity. We now wish: (1) To establish that our endogenously labelled pyrogens are homogeneous, and to make them so if they are not. (2) To confirm that highly purified pyrogens retain LAF activity. (3) To confirm our preliminary evidence that the type of pyrogen secreted by a macrophage is a function of its location in the body and of its state of activation. (4) To confirm our preliminary evidence that neutrophils are not a soucre of endogenous pyrogens, using a wider range of stimuli. (5) To determine whether our purified endogeous pyrogens have non-pyrogenic actions other than LAF, and in particular whether they cause the release of proteolytic enzymes from cells. (6) To inject purified endogeous pyrogens directly into anterior hypothalamic nuclei, and study the effects on body temperature and other acute phase reactions. (7) To attempt to raise an antibody to the second endogenous pyrogen. (8) To split the pyrogen molecules with cyanogen bromide, and other reagents, in the hope of generating biologically active fragments, and also to see whether the apparently unrelated pyrogens have any sequences in common. (9) To radiolabel the pyrogen for which we have antibody with 14C acetic anhydride, and develop a radio-immunoassay.